Phorbol esters enhance exocytosis from chromaffin cells by two mechanisms.
Treatment with phorbol esters such as 12-O-tetradecanoylphorbol acetate (TPA) rapidly enhances [3H]norepinephrine secretion from digitonin-permeabilized adrenal chromaffin cells. When TPA treatment was prolonged for several hours, a second distinct enhancing effect was observed. This later enhancement was most prominent at intracellular Ca2+ concentrations of 3-30 microM, and did not require the continued presence of membrane-bound protein kinase C for its expression. The effect could be elicited by as little as 30-min exposure to TPA, followed by several hours in TPA-free medium. This effect of TPA was blocked by actinomycin D and cycloheximide, indicating a requirement for RNA and protein synthesis. Similar effects were seen when intact cells that had been pretreated with TPA were stimulated to secrete by depolarizing concentrations of K+. Thus, protein kinase C enhances secretion by two mechanisms. One is rapid and probably reflects the effects of immediate protein phosphorylation. The other occurs over several hours and requires gene transcription and protein synthesis.
Bittner
M A
MA
Department of Pharmacology, University of Michigan Medical School, Ann Arbor 48109-0626.
Holz
R W
RW
D000313:Adrenal Medulla / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002417:Cattle; D002463:Cell Membrane Permeability; D002478:Cells, Cultured; D004072:Digitonin; D005089:Exocytosis / Q000187:drug effects*; D007700:Kinetics; D009638:Norepinephrine / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D004072:Digitonin; D013755:Tetradecanoylphorbol Acetate; D011188:Potassium; D009638:Norepinephrine